Dynamic Changes In Cerebral Blood Flow Research Articles

Continuous non-invasive estimates of cerebral blood flow using electrocardiography signals: a feasibility study

This paper describes a potential method to detect changes in cerebral blood flow (CBF) using electrocardiography (ECG) signals, measured across scalp electrodes with reference to the same signal across the chest—a metric we term the Electrocardiography Brain Perfusion index (EBPi). We investigated the feasibility of EBPi to monitor CBF changes in response to specific tasks. Twenty healthy volunteers wore a head-mounted device to monitor EBPi and electroencephalography (EEG) during tasks known to alter CBF. Transcranial Doppler (TCD) ultrasound measurements provided ground-truth estimates of CBF. Statistical analyses were applied to EBPi, TCD right middle cerebral artery blood flow velocity (rMCAv) and EEG relative Alpha (rAlpha) data to detect significant task-induced changes and correlations. Breath-holding and aerobic exercise induced highly significant increases in EBPi and TCD rMCAv (p < 0.01). Verbal fluency also increased both measures, however the increase was only significant for EBPi (p < 0.05). Hyperventilation induced a highly significant decrease in TCD rMCAv (p < 0.01) but EBPi was unchanged. Combining all tasks, EBPi exhibited a highly significant, weak positive correlation with TCD rMCAv (r = 0.27, p < 0.01) and the Pearson coefficient between EBPi and rAlpha was r = − 0.09 (p = 0.05). EBPi appears to be responsive to dynamic changes in CBF and, can enable practical, continuous monitoring. CBF is a key parameter of brain health and function but is not easily measured in a practical, continuous, non-invasive fashion. EBPi may have important clinical implications in this context for stroke monitoring and management. Additional studies are required to support this claim.

Early Thalamocortical Reperfusion Leads to Neurologic Recovery in a Rodent Cardiac Arrest Model.

Cerebral blood flow (CBF) plays an important role in neurological recovery after cardiac arrest (CA) resuscitation. However, the variations of CBF recovery in distinct brain regions and its correlation with neurologic recovery after return of spontaneous circulation (ROSC) have not been characterized. This study aimed to investigate the characteristics of regional cerebral reperfusion following resuscitation in predicting neurological recovery. Twelve adult male Wistar rats were studied, ten resuscitated from 7-min asphyxial CA and two uninjured rats, which were designated as healthy controls (HCs). Dynamic changes in CBF in the cerebral cortex, hippocampus, thalamus, brainstem, and cerebellum were assessed by pseudocontinuous arterial spin labeling magnetic resonance imaging, starting at 60min after ROSC to 156min (or time to spontaneous arousal). Neurologic outcomes were evaluated by the neurologic deficit scale at 24h post-ROSC in a blinded manner. Correlations between regional CBF (rCBF) and neurological recovery were undertaken. All post-CA animals were found to be nonresponsive during the 60-156min post ROSC, with reductions in rCBF by 24-42% compared with HC. Analyses of rCBF during the post-ROSC time window from 60 to 156min showed the rCBF recovery of hippocampus and thalamus were positively associated with better neurological outcomes (rs = 0.82, p = 0.004 and rs = 0.73, p < 0.001, respectively). During 96min before arousal, thalamic and cortical rCBF exhibited positive correlations with neurological recovery (rs = 0.80, p < 0.001 and rs = 0.65, p < 0.001, respectively); for predicting a favorable neurological outcome, the thalamic rCBF threshold was above 50.84ml/100g/min (34% of HC) (area under the curve of 0.96), whereas the cortical rCBF threshold was above 60.43ml/100g/min (38% of HC) (area under the curve of 0.88). Early magnetic resonance imaging analyses showed early rCBF recovery in thalamus, hippocampus, and cortex post ROSC was positively correlated with neurological outcomes at 24h. Our findings suggest new translational insights into the regional reperfusion and the time window that may be critical in neurological recovery and warrant further validation.

Disrupted Regional Cerebral Blood Flow and Functional Connectivity in Pontine Infarction: A Longitudinal MRI Study.

Abnormal cerebral blood flow (CBF) and resting-state functional connectivity (rs-FC) are sensitive biomarkers of disease progression and prognosis. This study investigated neural underpinnings of motor and cognitive recovery by longitudinally studying the changes of CBF and FC in pontine infarction (PI). Twenty patients underwent three-dimensional pseudo-continuous arterial spin labeling (3D-pcASL), resting-state functional magnetic resonance imaging (rs-fMRI) scans, and behavioral assessments at 1 week, 1, 3, and 6 months after stroke. Twenty normal control (NC) subjects underwent the same examination once. First, we investigated CBF changes in the acute stage, and longitudinal changes from 1 week to 6 months after PI. Brain regions with longitudinal CBF changes were then used as seeds to investigate longitudinal FC alterations during the follow-up period. Compared with NC, patients in the left PI (LPI) and right PI (RPI) groups showed significant CBF alterations in the bilateral cerebellum and some supratentorial brain regions at the baseline stage. Longitudinal analysis revealed that altered CBF values in the right supramarginal (SMG_R) for the LPI group, while the RPI group showed significantly dynamic changes of CBF in the left calcarine sulcus (CAL_L), middle occipital gyrus (MOG_L), and right supplementary motor area (SMA_R). Using the SMG_R as the seed in the LPI group, FC changes were found in the MOG_L, middle temporal gyrus (MTG_L), and prefrontal lobe (IFG_L). Correlation analysis showed that longitudinal CBF changes in the SMG_R and FC values between the SMG_R and MOG_L were associated with motor and memory scores in the LPI group, and longitudinal CBF changes in the CAL_L and SMA_R were related to memory and motor recovery in the RPI group. These longitudinal CBF and accompany FC alterations may provide insights into the neural mechanism underlying functional recovery after PI, including that of motor and cognitive functions.

Simultaneous monitoring of cerebral perfusion and cytochrome c oxidase by combining broadband near-infrared spectroscopy and diffuse correlation spectroscopy.

Preterm infants born with very low birth weights are at a high risk of brain injury, in part because the premature brain is believed to be prone to periods of low cerebral blood flow (CBF). Tissue damage is likely to occur if reduction in CBF is sufficient to impair cerebral energy metabolism for extended periods. Therefore, a neuromonitoring method that can detect reductions in CBF, large enough to affect metabolism, could alert the neonatal intensive care team before injury occurs. In this report, we present the development of an optical system that combines diffuse correlation spectroscopy (DCS) for monitoring CBF and broadband near-infrared spectroscopy (B-NIRS) for monitoring the oxidation state of cytochrome c oxidase (oxCCO) – a key biomarker of oxidative metabolism. The hybrid instrument includes a multiplexing system to enable concomitant DCS and B-NIRS measurements while avoiding crosstalk between the two subsystems. The ability of the instrument to monitor dynamic changes in CBF and oxCCO was demonstrated in a piglet model of neonatal hypoxia-ischemia (HI). Experiments conducted in eight animals, including two controls, showed that oxCCO exhibited a delayed response to ischemia while CBF and tissue oxygenation (StO2) responses were instantaneous. These findings suggest that simultaneous neuromonitoring of perfusion and metabolism could provide critical information regarding clinically significant hemodynamic events prior to the onset of brain injury.

Chronic cerebral hypoperfusion induces vascular plasticity and hemodynamics but also neuronal degeneration and cognitive impairment.

Chronic cerebral hypoperfusion (CCH) induces cognitive impairment, but the compensative mechanism of cerebral blood flow (CBF) is not fully understood. The present study mainly investigated dynamic changes in CBF, angiogenesis, and cellular pathology in the cortex, the striatum, and the cerebellum, and also studied cognitive impairment of rats induced by bilateral common carotid artery occlusion (BCCAO). Magnetic resonance imaging (MRI) techniques, immunochemistry, and Morris water maze were employed to the study. The CBF of the cortex, striatum, and cerebellum dramatically decreased after right common carotid artery occlusion (RCCAO), and remained lower level at 2 weeks after BCCAO. It returned to the sham level from 3 to 6 weeks companied by the dilation of vertebral arteries after BCCAO. The number of microvessels declined at 2, 3, and 4 weeks but increased at 6 weeks after BCCAO. Neuronal degeneration occurred in the cortex and striatum from 2 to 6 weeks, but the number of glial cells dramatically increased at 4 weeks after BCCAO. Cognitive impairment of ischemic rats was directly related to ischemic duration. Our results suggest that CCH induces a compensative mechanism attempting to maintain optimal CBF to the brain. However, this limited compensation cannot prevent neuronal loss and cognitive impairment after permanent ischemia.

Cerebral Hemodynamics at Altitude: Effects of Hyperventilation and Acclimatization on Cerebral Blood Flow and Oxygenation

Alterations in cerebral blood flow (CBF) and cerebral oxygenation are implicated in altitude-associated diseases. We assessed the dynamic changes in CBF and peripheral and cerebral oxygenation engendered by ascent to altitude with partial acclimatization and hyperventilation using a combination of near-infrared spectroscopy, transcranial Doppler ultrasound, and diffuse correlation spectroscopy. Peripheral (Spo2) and cerebral (Scto2) oxygenation, end-tidal carbon dioxide (ETCO2), and cerebral hemodynamics were studied in 12 subjects using transcranial Doppler and diffuse correlation spectroscopy (DCS) at 75 m and then 2 days and 7 days after ascending to 4559 m above sea level. After obtaining baseline measurements, subjects hyperventilated to reduce baseline ETCO2 by 50%, and a further set of measurements were obtained. Cerebral oxygenation and peripheral oxygenation showed a divergent response, with cerebral oxygenation decreasing at day 2 and decreasing further at day 7 at altitude, whereas peripheral oxygenation decreased on day 2 before partially rebounding on day 7. Cerebral oxygenation decreased after hyperventilation at sea level (Scto2 from 68.8% to 63.5%; P<.001), increased after hyperventilation after 2 days at altitude (Scto2 from 65.6% to 69.9%; P=.001), and did not change after hyperventilation after 7 days at altitude (Scto2 from 62.2% to 63.3%; P=.35). An intensification of the normal cerebral hypocapnic vasoconstrictive response occurred after partial acclimatization in the setting of divergent peripheral and cerebral oxygenation. This may help explain why hyperventilation fails to improve cerebral oxygenation after partial acclimatization as it does after initial ascent. The use of DCS is feasible at altitude and provides a direct measure of CBF indices with high temporal resolution.

Noninvasive Optical Measurement of Cerebral Blood Flow in Mice Using Molecular Dynamics Analysis of Indocyanine Green

In preclinical studies of ischemic brain disorders, it is crucial to measure cerebral blood flow (CBF); however, this requires radiological techniques with heavy instrumentation or invasive procedures. Here, we propose a noninvasive and easy-to-use optical imaging technique for measuring CBF in experimental small animals. Mice were injected with indocyanine green (ICG) via tail-vein catheterization. Time-series near-infrared fluorescence signals excited by 760 nm light-emitting diodes were imaged overhead by a charge-coupled device coupled with an 830 nm bandpass-filter. We calculated four CBF parameters including arrival time, rising time and mean transit time of a bolus and blood flow index based on time and intensity information of ICG fluorescence dynamics. CBF maps were generated using the parameters to estimate the status of CBF, and they dominantly represented intracerebral blood flows in mice even in the presence of an intact skull and scalp. We demonstrated that this noninvasive optical imaging technique successfully detected reduced local CBF during middle cerebral artery occlusion. We further showed that the proposed method is sufficiently sensitive to detect the differences between CBF status in mice anesthetized with either isoflurane or ketamine–xylazine, and monitor the dynamic changes in CBF after reperfusion during transient middle cerebral artery occlusion. The near-infrared optical imaging of ICG fluorescence combined with a time-series analysis of the molecular dynamics can be a useful noninvasive tool for preclinical studies of brain ischemia.

Noninvasive optical evaluation of spontaneous low frequency oscillations in cerebral hemodynamics

Spontaneous low frequency oscillations (LFOs) around 0.1 Hz have been observed in mean arterial pressure (MAP) and cerebral blood flow velocity (CBFV). Previous studies have shown that cerebral autoregulation in major arteries can be assessed by quantification of the phase shift between LFOs of MAP and CBFV. However, many cerebral diseases are associated with abnormal microvasculature and tissue dysfunction in brain, and quantification of these abnormalities requires direct measurement of cerebral tissue hemodynamics. This pilot study used a novel hybrid near-infrared diffuse optical instrument to noninvasively and simultaneously detect LFOs of cerebral blood flow (CBF) and cerebral oxygenation (i.e., oxygenated/deoxygenated/total hemoglobin concentration: [HbO(2)]/[Hb]/THC) in human prefrontal cortex. Using the hybrid instrument and a finger plethysmograph, the dynamic changes of CBF, [HbO(2)], [Hb], THC and MAP were concurrently measured in 15 healthy subjects at rest, during 70° head-up-tilting (HUT) and during enforced breathing at 0.1 Hz. The LFOs were extracted from the measured variables using power spectral analysis, and the phase shifts and coherences of LFOs between MAP and each of the measured hemodynamic variables were calculated from the corresponding transfer functions. Levels of coherence (>0.4) were used to judge the success of LFO measurements. We found that CBF, [HbO(2)] and THC were reliable hemodynamic parameters in detecting LFOs and HUT was the most robust and stable protocol for quantifying phase shifts of hemodynamic LFOs. Comparing with other relevant studies, similar success rates for detecting cerebral LFOs have been achieved in our study. The phase shifts of LFOs in CBF were also close to those in CBFV reported by other groups, although the results in cerebral oxygenation measurements during enforced breathing varied across studies. Future study will investigate cerebral LFOs in patients with cerebral impairment and evaluate their cerebral autoregulation capabilities and neurocognitive functions via the quantification of LFO phase shifts.

Dynamic relationship between changes in CBF and CBV during somatosensory stimulation: Implications for calibrated fMRI

The relationship between dynamic changes in cerebral blood flow (CBF) and volume (CBV) are very important for calibrating fMRI so that changes in oxidative metabolism can be determined 1. Although recent animal studies 2, 3 have investigated dynamic changes in CBF and CBV (CBF/CBF and CBV/CBV), the studies were limited by use of either non-quantitative methods or the CBF and CBV data had different spatial resolutions. Here towards the goal of calculating dynamic changes in cerebral metabolic rate for oxygen consumption (CMRo2) quantitatively, we demonstrate the combined method of the modified functional MRI for CBF 4 with contrast agent for CBV 5 to clarify the relationship between dynamic CBF/CBF and CBV/CBV of rat somatosensory cortex during forepaw stimulation with different stimulus duration (4,8,16,32 seconds). The figure 1 shows the relationship between dynamic CBF/CBF and CBV/CBV for two stimulus duration (4 (blue) and 16 (red) seconds). The filled and opened symbols represent the period of transition from stimulus onset to peak and transition from stimulus offset to baseline, respectively. The dotted lines show the value of the parameter ranging from 0.05 to 0.4 in CBV=CBF∧. The relationship between dynamic CBF/CBF and CBV/CBV was different throughout different stimulus durations and became complex as the stimulus duration became longer. The values of a ranged from 0.05 to 0.15 during transition from stimulus onset to a peak, whereas the value ranged from 0.15 to 0.45 during transition to baseline after stimulus offset. Thus the Grubb's power exponent, =0.38 6, should be used with caution when being used for predicting changes in CMRo2 during transition 7 and even steady state 8 since the values of a ranged from 0.10 to 0.25 under steady state throughout stimulus durations. This is the first study to directly investigate the relationship between the dynamic changes in CBF and CBV during transition periods (i.e. onset and offset of stimulation) using only MRI methods, which allow us to measure the transient changes with same spatial and temporal resolution in same subject. The modified fMRI method with contrast agent has a great potential to predict the dynamic changes in CMRo2 without any further perturbations or assumption.

Effects of 7-nitroindazole and N-nitro- l-arginine methyl ester on changes in cerebral blood flow and nitric oxide production preceding development of hyperbaric oxygen-induced seizures in rats

Hyperbaric oxygen (HBO 2) exposure induces increases in cerebral blood flow (CBF) and extracellular concentrations of nitric oxide (NO) that precede the appearance of central nervous system toxicity, which may manifest as convulsions. To elucidate the origins of NO production during HBO 2 exposure, we examined the effects of the selective neuronal NO synthase (NOS) inhibitor, 7-nitroindazole (7-NI), and the non-selective NOS inhibitor, N-nitro- l-arginine methyl ester ( l-NAME), on changes in CBF and NO metabolites (NO x , nitrite and nitrate) using a laser Doppler flow probe and in vivo microdialysis techniques, respectively. Rats were anesthetized, artificially ventilated, and pressurized to 5 atmosphere absolute (ATA) with pure oxygen for 60 min. In rats treated with vehicle, CBF and NO x levels in the cortex increased to 201% and 239% of basal levels, respectively, before the onset of electrical discharges, measured by electroencephalogram. The increase in CBF and NO x was completely inhibited by 7-NI and l-NAME. Both drugs also inhibited the appearance of electrical discharges for 60 min. Dynamic changes in CBF and NO x were not significantly different between 7-NI and l-NAME. These findings suggest that neuronal NOS is the main mediator of NO production associated with increase in CBF leading to the appearance of electrical discharge during HBO 2 exposure.

121 Dynamic Changes In Cerebral Blood Flow During Selective Head Cooling In Newborn Piglets

Background/Aim: Selective head cooling (SHC) is a promising therapy for hypoxic-ischaemic brain damage (HIBD) in neonates. Disturbance of cerebral blood flow (CBF) plays an important role in neonatal HIBD. Safe application of SHC will depend on a better understanding of the effects of hypothermia on CBF which is influenced by temperature. This research aimed to study dynamic changes in CBF following SHC in newborn piglets.Methods: Sixteen newborn piglets, 5 to 7 day old, were randomly assigned to one of the following groups: SHC in normal piglets (n= 4), SHC after HI (n= 6) and normal temperature after HI (n= 6). HI was induced using temporary occlusion of the bilateral carotid arteries and mechanical ventilation with low concentration of oxygen (6%) for 30 minutes. In SHC nasopharyngeal temperature was reduced to 35 °C, and then to 32 °C. During HI and SHC, heart rate, respiratory rate, arteria blood pressure, SpO2, blood glucose and haemoglobin were monitored. CBF was measured with colour microspheres before HI (as baseline) and 2, 4 (35 °C), 6 (32 °C ) and 8 hours (rewarming) after HI.Results: During HI and SHC, no differences in arteria blood pressure, SpO2, blood glucose and haemoglobin were seen among the three groups studied. In normal piglets during SHC, global CBF decreased to 68% and 50% of baseline at 35 °C and 32 °C, respectively, particularly in temporal lobe, parietal lobe, brainstem and cerebellum. In normal temperature newborn piglets after HI, global CBF was decreased to 78% and 60% of baseline at 2h and 4h, respectively, after HI, particularly in temporal lobe, parietal lobe, hippocampus and thalamus. In SHC piglets after HI, similar decrease in global CBF was observed at the same time point at 35 °C and 32 °C, but local CBF was increased at 35 °C, particularly in the hippocampus, striatum and thalamus. At 32 °C, however, local CBF tended to decrease, particularly in the cerebellum, brainstem and parietal lobe.Conclusion: Global CBF was decreased in piglets at 2h and 4h after HI. The decrease was not influenced by SHC, although global CBF was decreased in normal piglets during SHC. Local CBF in HI piglets during SHC was improved at 35 °C, and tended to decrease when temperature was reduced to 32 °C. Thus, after HI although SHC does not improve global CBF, it improves local CBF when the temperature remains at 35 °C.

Experimental intracerebral hemorrhage in the mouse: histological, behavioral, and hemodynamic characterization of a double-injection model.

A major limitation of intracerebral hemorrhage (ICH) research is the lack of reproducible animal models. The present study was conducted to validate in the mouse the double-injection method of ICH initially developed in the rat. We investigated the effect of intrastriatal injection of blood or cerebrospinal fluid (CSF) on cerebral blood flow (CBF), neurological score, hematoma volume, and brain swelling. Male C57BL/6 mice were anesthetized with halothane/nitrous oxide delivered by face mask. Rectal and cranial temperatures were regulated at 37 degrees C to 37.5 degrees C. Mice were placed in a stereotactic frame, and a 30-gauge stainless steel cannula was introduced through a burr hole into the left striatum. Each mouse received a 5-microL injection of either whole blood or CSF (over 3 minutes), followed 7 minutes later by 10 microL injected over 5 minutes. The injection cannula was slowly withdrawn 10 minutes after the second injection. Control mice had only cannula insertion. CBF was studied by laser Doppler perfusion imaging. Neurological status was evaluated on days 1 and 2. After 2 days, hematoma volume and brain swelling were calculated. Physiological values were stable. Mice with ICH but not those with CSF or cannula alone had a marked, persistent neurological deficit and a highly reproducible hematoma, whose mean+/-SEM volume was 2.0+/-0.2 mm3 compared with a lesion size of 0.2+/-0.1 mm3 in mice with CSF. Residual swelling of the ipsilateral hemisphere at 48 hours was 5.7% in the hematoma and 1.5% in the CSF groups. Relative CBF in the neocortex ipsilateral to the injection site declined by approximately 45% to 60% during the first 20 minutes after cannula insertion/injection in all groups but began to renormalize at approximately 25 to 30 minutes in the CSF and cannula-only groups; in the hematoma group, cortical hypoperfusion of approximately 35% to 50% persisted during the 90-minute measurement period. The present ICH model in mice produces a consistent neurological deficit, hypoperfusion, hematoma volume, and brain swelling. This model closely mimics human hypertensive basal ganglionic ICH and should be useful for the evaluation of pharmaceutical therapies. Laser Doppler perfusion imaging is a useful new technique to quantify relative CBF changes and can be used for studies of dynamic changes of CBF in this in vivo model of ICH in mice.

Dynamic changes of CBF, CMRO 2, OEF, CMR glc, CBV and ADC during neuronal suppression due to hypothermia

The objective of this study was to test that hypothermia improves the outcome of an acute ischemic stroke. In order to test the hypothesis that hypothermia (32 °C) improves the outcome by effecting the global cerebral reduction of oxygen consumption when the blood flow is already low, we investigated the sequential changes of physiological variables during hypothermia using positron emission tomography (PET) and diffusion-weighted magnetic resonance imaging (DW-MRI) in pigs. The cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO 2) decreased significantly to within 50% of the baseline in 3 and 5 h as functions of time, thereby lowering the viability threshold of the brain tissue. The oxygen extraction fraction (OEF) was significantly elevated to 140% of the baseline in 4 h, indicating a reduction in the driving pressure of oxygen delivery in response to the reduced metabolic need, and then it gradually returned so that it was once again level with the baseline. The cerebral metabolic rate of glucose (CMR glc), the cerebral blood volume (CBV), and apparent diffusion coefficient (ADC) decreased to 75%, 72% and 80% of the baseline after 6 h of hypothermia in response to the lowered metabolism for maintenance of cellular integrity, and the diminution of intracranial pressure. The results of ischemia show that rapid cooling of the brain to 32 °C significantly increases the survival of tissue at risk.

Flow quantification in the superior sagittal sinus using magnetic resonance

To date, the intracerebral veins and venous sinuses have not been amenable to noninvasive study. We describe a magnetic resonance (MR) technique using "bolus tracking" for rapid imaging and measurement of cerebral venous flow. We specifically applied the technique to the superior sagittal sinus, but it can be used for evaluation of other cerebral venous structures. In 10 healthy subjects and 21 patients referred for MR brain studies, mean flow was 420 ml/min. There was a significant inverse correlation between blood flow and age. There were dynamic changes in cerebral blood flow (CBF) during hyperventilation and hypercapnia. Since the cerebral cortex drains almost exclusively to the superior sagittal sinus, these flow measurements represent an index of global CBF. MR flow quantification provides a new means for assessing dynamic changes in CBF, and may prove useful for monitoring the effects of various disease processes and pharmaceutical agents on CBF.